Treatment of endometriosis with mifepristone mediated by nanostructured lipid carriers

Mifepristone, a progesterone receptor antagonist, was initially used to terminate early pregnancy. As scientific research advanced, it emerged to be effective in the treatment of various tumors and tumor-like conditions such as endometriosis. Despite the therapeutic potential of mifepristone, its therapeutic effect is still far from ideal because the drug is difficult to dissolve and to accumulate in the target tissue sites. To address this issue, mifepristone-loaded nanostructured lipid carriers (Mif-NLC) were prepared by a simple solvent diffusion method and their anti-endometriosis performance and mechanisms were initially investigated. By optimizing the preparation protocol, we obtained uniform and spheroidal Mif-NLC with an average particle size of 280 nm. The encapsulation rate and drug loading capacity were 64.67% ± 0.15% and 2.7% ± 0.014%, respectively, as measured by UV spectrophotometry. The in vitro release kinetics indicated that mifepristone was released from NLC in a sustained-release manner. Compared with free mifepristone, Mif-NLC exhibited enhanced cellular uptake and inhibition of invasion activity in primary mesenchymal cells of endometriosis. A certain reduction in the size of endometriotic cysts was observed in animals compared to controls. The induction of autophagy via Mif-NLC may serve as the molecular mechanism underlying this effect. Furthermore, observation of uterine structures showed negligible toxic effects. This suggested that mifepristone encapsulated in NLC can improve its bioavailability and anti-endometriosis efficacy, which provided a new strategy for the treatment of endometriosis. Graphical Abstract Similar content being viewed by others Data availability The collected and analyzed datasets during the current study are available from the corresponding author on reasonable request.

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We are thankful for the funding from the National Natural Science Foundation of China (82071616 and 82103505) and the Nature Science Foundation of Zhejiang province (LY19H040011 and LQ22H040005). Author information Authors and Affiliations Contributions All authors contributed to the manuscript. Conceptualization: Jingjing Yan and Mengdan Zhao. Formal analysis and investigation: Yujie Peng and Shiyao Huang. Methodology and data curation: Jingjing Yan, Yujie Peng, Shiyao Huang, and Meng Zhang. Funding acquisition: Mengdan Zhao, and Meng Zhang. Writing—original draft: Jingjing Yan. Writing—review and editing: Yue Chen and Weidong Fei. Supervision: Caihong Zheng, Meng Zhang and Mengdan Zhao. Corresponding authors Ethics declarations Ethics approval and consent to participate The animal experiment was conducted in line with the ethical guidelines set forth by the Experimental Animal Ethics Committee of Zhejiang University and the approval no. for animal protocol is ZJCLA-IACUC-20010072. Consent for publication The authors declare that they have provided their consent for publishing this manuscript. Competing interests The authors report no conflicts of interest in this work. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Yan, J., Peng, Y., Huang, S. et al. Treatment of endometriosis with mifepristone mediated by nanostructured lipid carriers. Drug Deliv. and Transl. Res. 15, 1181–1192 (2025). https://doi.org/10.1007/s13346-024-01661-3 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s13346-024-01661-3